53 year-old female with well-circumscribed right renal mass

Author
Katrina Collins, MD
Indiana University School of Medicine, Indianapolis, IN

Summary of clinical history
53-year-old female with well-circumscribed right renal mass, partial nephrectomy was performed

Gross findings
4.7 cm tan, well-circumscribed and focally hemorrhagic mass, confined to kidney

Microscopic findings
The tumor is well-circumscribed but not encapsulated. Tumor is composed of tightly packed tubules. Tumor nuclei are round or oval with occasional grooves and no obvious nucleoli are present and the cell cytoplasm is scant. In some areas, curvilinear tubules imparting papillary appearance are seen. Psammomatous calcifications are abundant.

Immunohistochemical findings
Positive: WT1, CD57, BRAF, PAX8
Negative: CK7, AMACR

Test yourself. What diagnosis would you give to this case?

• Papillary renal cell carcinoma, solid variant
• Nephroblastoma (Wilms tumor), epithelial predominant
• Metanephric adenoma
• Metanephric-like ALK rearranged renal cell carcinoma
• Metastatic thyroid carcinoma, poorly differentiated

The main differential diagnoses in this case includes metanephric adenoma, the solid variant of papillary RCC, and adult Wilms tumor. An intriguing contradiction lies in the fact that while papillary RCC, a malignant tumor, is often encapsulated, metanephric adenoma, considered a benign tumor, typically lacks encapsulation. Wilms tumor typically exhibits two or three components — epithelial, blastema, and stromal elements — although monophasic cases are rare. Its cellular morphology appears less mature compared to metanephric adenoma, and it usually displays a higher mitotic rate.

Immunohistochemistry might prove helpful in distinguishing between metanephric adenoma and papillary RCC. Papillary RCC is positive for CK7, AMACR, and EMA, whereas metanephric adenoma usually does not show these markers. Metanephric adenoma may exhibit positivity for WT1, CD56, and CD57, while papillary RCC is usually negative for these markers. However, these immunomarkers are not useful in distinguishing metanephric adenoma from adult Wilms tumor, as they often share the same staining patterns.

Key differential diagnosis

Papillary renal cell carcinoma, particularly solid variant:

• Less tightly packed tubules and less basophilic, usually has foamy macrophages
• Vimentin+, PAX8+, CK7+, AMACR+, WT1-, CD57-, BRAF-

Metanephric-like ALK rearranged renal cell carcinoma:

• Similar morphology to metanephric adenoma
• Vimentin+, PAX8+, CK7+, ALK+, AMACR+, BRAF-, CD57-, WT1-

Nephroblastoma:

• Difficult to differentiate if tumor is monophasic, (blastema component only)
• PAX8+, WT1+, vimentin-, CD57-, BRAF-

Metastatic thyroid carcinoma, particularly poorly differentiated:

• Malignant cells with nuclear grooves and pseudonuclear inclusions
• PAX8+, TTF1+, BRAF+, WT1-

References

Kinney SN, Eble JN, Hes O, Williamson SR, Grignon DJ, Wang M, Zhang S, Baldrige LA, Martignoni G, Brunelli M, Wang L, Comperat E, Fan R, Montironi R, MacLennan GT, Cheng L. Metanephric adenoma: the utility of immunohistochemical and cytogenetic analyses in differential diagnosis, including solid variant papillary renal cell carcinoma and epithelial-predominant nephroblastoma. Mod Pathol. 2015;28(9):1236-1248. doi:10.1038/modpathol.2015.81

Pinto A, Signoretti S, Hirsch MS, Barletta JA. Immunohistochemical staining for BRAF V600E supports the diagnosis of metanephric adenoma. Histopathology. 2015 May;66(6):901-4. doi: 10.1111/his.12509. Epub 2015 Jan 23. PMID: 25130952.

Udager AM, Pan J, Magers MJ, Palapattu GS, Morgan TM, Montgomery JS, Weizer AZ, Hafez KS, Miller DC, Wolf JS Jr, McHugh JB, Chinnaiyan AM, Dhanasekaran SM, Mehra R. Molecular and immunohistochemical characterization reveals novel BRAF mutations in metanephric adenoma. Am J Surg Pathol. 2015;39(4):549-557. doi:10.1097/PAS.0000000000000377

Kuroda N, Trpkov K, Gao Y, Tretiakova M, Liu YJ, Ulamec M, Takeuchi K, Agaimy A, Przybycin C, Magi-Galluzzi C, Fushimi S, Kojima F, Sibony M, Hang JF, Pan CC, Yilmaz A, Siadat F, Sugawara E, Just PA, Ptakova N, Hes O. ALK rearranged renal cell carcinoma (ALK-RCC): a multi-institutional study of twelve cases with identification of novel partner genes CLIP1, KIF5B and KIAA1217. Mod Pathol. 2020;33(12):2564-2579. doi:10.1038/s41379-020-0578-0